Lehoux J G, Lefebvre A, de Medicis E, Bastin M, Bélisle S, Bellabarba D
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
J Steroid Biochem. 1987;27(4-6):1151-60. doi: 10.1016/0022-4731(87)90202-0.
Previous studies have established that under normal conditions, adrenal HMG-CoA reductase activity is higher in hamsters than in rats and humans. The hamster reductase activity follows a diurnal rhythm corresponding to that of plasma ACTH and glucocorticoids [Endocrinology 107 (1980) 215] but not to that of aldosterone. ACTH treatments to hamsters increased reductase activity after a latency of 60 min; this enhancement was prevented by cycloheximide [J. steroid Biochem. 24 (1986) 325]. Immunotitration and immunoblotting studies confirmed that ACTH caused an increase in reductase protein synthesis. In rats, long-term (1-9 days) and short-term (3 h) treatments with ACTH also induced increase in adrenal HMG-CoA reductase activity and reductase protein. In the presence of iodoacetamide and inhibitors of proteolytic enzyme, a main specific band of enzyme was evinced in the area of 102 +/- 6 kDaMr, by Western blotting, for both hamster homogenate and microsomal preparations (Endocrinology, 120 (1987]. Similarly Mr values were found with rat adrenal preparations. The concentration of mRNA, analyzed using the c-DNA pRed-10 coding for the Chinese hamster ovary reductase, was increased in adrenals of hamsters treated with ACTH. The reductase mRNA levels also fluctuated during the day in parallel with those of reductase activity and reductase protein. In conclusion, these results indicate that ACTH and other conditions inducing a change in hamster adrenal HMG-CoA reductase activity provoke parallel changes in reductase mRNA and reductase protein content. ACTH acts on the adrenal reductase of species synthesizing large as well as small quantities of cholesterol, thus indicating the general importance of this hormonal control.
以往的研究表明，在正常情况下，仓鼠肾上腺HMG-CoA还原酶活性高于大鼠和人类。仓鼠的还原酶活性呈现出与血浆促肾上腺皮质激素（ACTH）和糖皮质激素相应的昼夜节律[《内分泌学》107 (1980) 215]，但与醛固酮的节律不同。对仓鼠进行ACTH处理后，经过60分钟的潜伏期，还原酶活性增加；环己酰亚胺可阻止这种增强作用[《类固醇生物化学杂志》24 (1986) 325]。免疫滴定和免疫印迹研究证实，ACTH导致还原酶蛋白合成增加。在大鼠中，长期（1 - 9天）和短期（3小时）给予ACTH处理，也会诱导肾上腺HMG-CoA还原酶活性和还原酶蛋白增加。在碘乙酰胺和蛋白水解酶抑制剂存在的情况下，通过蛋白质印迹法，在仓鼠匀浆和微粒体制剂中，均在102 +/- 6 kDaMr区域显示出一条主要的酶特异性条带（《内分泌学》，120 (1987)）。大鼠肾上腺制剂也得到了类似的Mr值。使用编码中国仓鼠卵巢还原酶的c-DNA pRed-10分析mRNA浓度，发现ACTH处理的仓鼠肾上腺中mRNA浓度增加。还原酶mRNA水平在一天中也与还原酶活性和还原酶蛋白水平平行波动。总之这些结果表明，ACTH和其他导致仓鼠肾上腺HMG-CoA还原酶活性变化的条件，会引起还原酶mRNA和还原酶蛋白含量的平行变化。ACTH作用于合成大量和少量胆固醇的物种的肾上腺还原酶，因此表明这种激素调控具有普遍重要性。
